The goal of our research is to understand some of the mechanisms by which gene expression is modulated in normal eukaryotic cells and the mechanisms by which this control becomes aberrant following neoplastic transformation. A number of different eukaryotic genes are under study which influence the structure and function of the cell membrane; these include members of the ras family (cloned both from mammalian cells and yeast), a major secretory protein of rats (alpha-2 microglobulin), and influenza virus hemagglutinin. During the past year, these genes have been cloned and expressed in a variety of different vectors in both yeast and mammalian cells. Mutations have been introduced at specific sites into the genes, and the effect of these mutations on the function of the proteins and their pathways of transportation through the cell have been measured and analyzed. We have also begun to exploit the possibilities of using yeasts as a eukaryotic system in which the function of genes that are (1)\important in controlling growth of mammalian cells, and (2)\conserved over long periods of evolutionary time can be determined. ras genes clearly fall into this category, and we are presently analyzing the functions of the members of this family that are naturally present in yeasts, as well as those from exotic organisms that have been artifically introduced into yeast. (V)